Evaluating the association of biallelic OGDHL variants with significant phenotypic heterogeneity.

ABSTRACT:

Background

Biallelic variants in OGDHL, encoding part of the α-ketoglutarate dehydrogenase complex, have been associated with highly heterogeneous neurological and neurodevelopmental disorders. However, the validity of this association remains to be confirmed. A second OGDHL patient cohort was recruited to carefully assess the gene-disease relationship.

Methods

Using an unbiased genotype-first approach, we screened large, multiethnic aggregated sequencing datasets worldwide for biallelic OGDHL variants. We used CRISPR/Cas9 to generate zebrafish knockouts of ogdhl, ogdh paralogs, and dhtkd1 to investigate functional relationships and impact during development. Functional complementation with patient variant transcripts was conducted to systematically assess protein functional

SUBMITTER: Lin SJ 

PROVIDER: S-EPMC10688095 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature